Drug – bio-affecting and body treating compositions – Antigen – epitope – or other immunospecific immunoeffector – Amino acid sequence disclosed in whole or in part; or...
Patent
1996-08-14
1998-04-14
Saunders, David
Drug, bio-affecting and body treating compositions
Antigen, epitope, or other immunospecific immunoeffector
Amino acid sequence disclosed in whole or in part; or...
4242781, 514 2, 514 21, 530412, 530380, A61K 3817, A61K 3802, C07K 200
Patent
active
057388482
DESCRIPTION:
BRIEF SUMMARY
This application is a 371 of PCT/AU95/00072.
TECHNICAL FIELD
This invention is directed to compounds which prevent rejection of transplanted tissue in a mammal, a method of isolating the compounds and a method of preventing rejection of transplanted tissue in a mammal.
BACKGROUND ART
Organ transplants, particularly kidney transplants, have become routine surgical procedures. However, transplants of organs such as heart, lung, pancreas or lower bowel are infrequently performed because of rejection of the transplanted organ by the recipient's immune system. Rejection is similarly a problem with kidney transplants.
An essential pre-requisite to transplantation is the screening of potential donors for identity of the donor histocompatibility complex with that of the recipient. However, with the exception of monozygotic twins, finding a donor with an identical histocompatibility complex is virtually impossible. Reliance must therefore be had on immunosuppressants so that the transplanted organ will not be rejected by the recipient's immune system.
Immunosuppressive compounds suitable for use in conjunction with organ transplantation include purine analogs such as 6-mercaptopurine, corticosteroids such as prednisone and prednisolone, antilymphocyte globulin, certain antibiotics such as cyclosporin A, and monoclonal antibodies specific for the IL-2 receptor. All of the above compounds have the disadvantage that they have general immunosuppressive effects. Hence, all tissues are damaged where rapid cell division is occurring.
Known immunosuppressive compounds also have undesirable side effects. This is particularly the case with the most widely used immunosuppressant cyclosporin A. Transplant recipients on cyclosporin A therapy invariably develop a cancer within 30 years of commencing therapy.
Another major drawback of immunosuppression with compounds such as cyclosporin A is the cost of therapy. Immunosuppression therapy with existing immunosuppressants must be maintained throughout the life of a transplant recipient. Cyclosporin A therapy currently costs about $1,000 per month per patient.
There is thus a pressing need for a compound which can be used to suppress rejection of a transplanted organ in a recipient but which does not have the disadvantages of the immunosuppressants currently used in conjunction with organ transplantation. Desirable properties of such a compound can be specified as follows: (i) relative specificity as an inhibitor of organ rejection but limited activity as a general immunosuppressant, (ii) an absence of undesirable side effects such as cell toxicity or carcinogenicity; and (iii) a relatively low cost or a biological activity which obviates long term therapy with the compound.
SUMMARY OF THE INVENTION
It is an object of this invention to provide compounds which suppress allograft rejection in a mammalian recipient and overcome the disadvantages of compounds presently used to prevent rejection of transplanted organs.
Further objects of the invention are to provide a method of identifying compounds which suppress allograft rejection in a mammalian subject, a method of isolating such compounds, and a method of suppressing allograft rejection.
In one aspect, the invention provides a protein which suppresses allograft rejection in a mammalian recipient, which protein is found in serum of a post liver transplantation subject and has a molecular weight selected from a molecular weight of about 10 kD, about 40 kD or about 87 kD, or is a homologue of a 10 kD, 40 kD or 87 kD protein found in serum of a post liver transplantation rat.
A preferred protein is a protein found in serum of a post orthotopic liver transplantation or re-transplantation rat which has the following N-terminal amino acid sequence:
______________________________________ V H G A D A E T A I V N G X I
(SEQ ID NO:1)
X S L A A T H M H G N (SEQ ID NO:2)
X E D I N F Q A F V E P H V
(SEQ ID NO:3)
______________________________________
In another aspect, the invention provides a method of identifying immunos
REFERENCES:
Burnham, NL. Am J Hosp Pharm. 51:210-218, Jan. 15, 1994.
Macy, E et al. J Allergy Clin Immunol. 83(5):871-875, May 1989.
J. Biochem vol. 107 No. 3 (1990), Shinomiya, T., et al. "Rat Liver Arginase Suppresses Mixed Lymphocyte Reaction", pp. 435-439.
Kiev Urology Institute, "Liver Allo-Transplant Detachment Prevention by Immunodepressant Therapy and Additional Proteinase Inhibitor" Derwent Abstract Accession No. 91-206472/28, Class B05, SU 1588420-A, 30 Aug. 1990 (Abstract Only).
Saunders David
VanderVegt F. Pierre
LandOfFree
Immunosuppressive compounds and method of preparing same does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Immunosuppressive compounds and method of preparing same, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Immunosuppressive compounds and method of preparing same will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-632602